| First Author | Liu S | Year | 2011 |
| Journal | Arthritis Rheum | Volume | 63 |
| Issue | 1 | Pages | 239-46 |
| PubMed ID | 20936632 | Mgi Jnum | J:171300 |
| Mgi Id | MGI:4949577 | Doi | 10.1002/art.30074 |
| Citation | Liu S, et al. (2011) CCN2 is required for bleomycin-induced skin fibrosis in mice. Arthritis Rheum 63(1):239-46 |
| abstractText | OBJECTIVE: No therapy for fibrotic disease is available. The proadhesive matricellular protein connective tissue growth factor CCN2 is a marker of fibrotic cells; however, the specific role of CCN2 in connective tissue biology in general and in fibrogenesis in particular is unclear. The aim of this study was to assess whether adult mice bearing a smooth muscle cell/fibroblast-specific deletion of CCN2 are resistant to bleomycin-induced skin scleroderma. METHODS: Cutaneous fibrosis was induced in mice by subcutaneous injection of bleomycin. Untreated control groups were injected with phosphate buffered saline. Mice bearing a fibroblast/smooth muscle cell-specific deletion of CCN2 were investigated for changes in dermal thickness, collagen content, and the number of alpha-smooth muscle actin (alpha-SMA)-positive cells. Dermal fibroblasts were isolated to assess whether the induction of collagen and alpha-SMA messenger RNA in response to transforming growth factor beta (TGFbeta) was impaired. RESULTS: The loss of CCN2 resulted in resistance to bleomycin-induced skin fibrosis. In response to bleomycin, wild-type mice possessed, but CCN2-deficient mice lacked, abundant alpha-SMA-expressing myofibroblasts within fibrotic lesions. Fibroblast responses to TGFbeta, a potent inducer of myofibroblast differentiation, were not affected. Collectively, these results indicate that CCN2 is essential for bleomycin-induced skin fibrosis, likely due to a defect in myofibroblast recruitment. CONCLUSION: These data indicate that therapeutic strategies that involve blocking CCN2 in vivo may be of benefit in combating fibrotic skin disease. |
